Heat shock proteins: in-depth information

Heat shock proteins and cancer

HSPs: How They Work

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In animal experiments, the ability of heat shock proteins (HSPs) to prevent cancer was found to be highly specific: HSPs from tumor X could immunize against tumor X, but not against tumor Y. Similarly, HSPs from tumor Y could immunize against tumor Y, but not against tumor X. Because HSPs are the same from person to person, it did not seem to make sense that these proteins could stimulate such specific reactions.

Finally, Dr. Pramod Srivastava showed that heat shock proteins alone could not specifically vaccinate against cancer — but they could when they were bound to short pieces of proteins called peptides. Neither HSPs nor the peptides by themselves worked — it was only the combination of HSPs plus the peptides that provided specific immunity against cancer. This means that the vaccines that prevented cancer in animal experiments contained HSPs that were bound to peptides.

Find out more about experiments with HSP cancer vaccines.

Heat shock proteins and immune response

Under normal conditions, heat shock proteins are not found outside the cell. But if a cancerous or infected cell has become so sick that it dies and its membrane bursts, all of the cell’s contents spill out, including heat shock proteins that are bound to peptides. These extracellular HSPs send a very strong ‘dange r signal’ to the immune system, instructing it to destroy the other diseased cells. This is how it works:

A sick cell dies and ruptures, spilling out the HSP-peptide complexes.
These extracellular complexes of HSPs and peptides are detected by circulating immune system cells called antigen-presenting cells (APCs). These APCs include cells called macrophages and dendritic cells.
The HSP complexes bind the CD91 receptor on the APC cell surface. The APC can then take in the HSP complexes.
Once the APCs have taken in the HSP complexes, they travel to the lymph nodes, which are clusters of immune system tissue that are distributed throughout the body.
In the lymph nodes, the APCs take the peptides that were associated with the HSPs and re-present them on the APC cell surface. These peptides are antigenic — meaning that they can stimulate an immune response.
In the lymph nodes, specialized immune cells called T cells ‘see’ these peptides and are then programmed to seek out cells bearing these specific, abnormal peptides.
Because every person and every cancer is different, the unique repertoire of antigenic peptides represents that individual patient’s specific cancer’s ‘fingerprint.’ The T cells are activated to target and destroy cancer cells bearing this fingerprint.

Learn more about our investigational products based on HSP technology:

Oncophage for cancer

AG-707 for genital herpes

HSP technology

Antigenics’ researchers have shown that the investigational vaccine Oncophage^® (vitespen; formerly HSPPC-96), which consists of the HSP-peptide complexes derived from a patient’s tumor, interacts with the immune system’s antigen-presenting cells at the site of injection. From this point on, the steps involved in triggering specific immune response appear to be the same as those believed to be triggered naturally when extracellular HSPs send a danger signal to the immune system. Specifically, the HSP complexes bind to the CD91 receptor on APCs, and are taken into the cells. The APCs then travel to the lymph nodes, where they re-present the antigenic peptides on their surfaces. This triggers a cancer-specific immune response, including stimulation of various immune cells and release of immune system substances called cytokines.

Learn more about other applications of HSP technology.

Read our white paper on HSP technology.